Journal Title
Title of Journal: Cardiovasc Drugs Ther
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Abbravation: Cardiovascular Drugs and Therapy
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Authors: Hiroyuki Takahama Hirokazu Shigematsu Tomohiro Asai Takashi Matsuzaki Shoji Sanada Hai Ying Fu Keiji Okuda Masaki Yamato Hiroshi Asanuma Yoshihiro Asano Masanori Asakura Naoto Oku Issei Komuro Masafumi Kitakaze Tetsuo Minamino
Publish Date: 2013/01/24
Volume: 27, Issue: 2, Pages: 125-132
Abstract
Although amiodarone is recognized as the most effective antiarrhythmic drug available it has negative hemodynamic effects Nanosized liposomes can accumulate in and selectively deliver drugs to ischemic/reperfused I/R myocardium which may augment drug effects and reduce side effects We investigated the effects of liposomal amiodarone on lethal arrhythmias and hemodynamic parameters in an ischemia/reperfusion rat modelWe prepared liposomal amiodarone mean diameter 113 ± 8 nm by a thinfilm method The left coronary artery of experimental rats was occluded for 5 min followed by reperfusion Ex vivo fluorescent imaging revealed that intravenously administered fluorescentlabeled nanosized beads accumulated in the I/R myocardium Amiodarone was measurable in samples from the I/R myocardium when liposomal amiodarone but not amiodarone was administered Although the intravenous administration of amiodarone 3 mg/kg or liposomal amiodarone 3 mg/kg reduced heart rate and systolic blood pressure compared with saline the decrease in heart rate or systolic blood pressure caused by liposomal amiodarone was smaller compared with a corresponding dose of free amiodarone The intravenous administration of liposomal amiodarone 3 mg/kg but not free amiodarone 3 mg/kg 5 min before ischemia showed a significantly reduced duration of lethal arrhythmias 18 ± 9 s and mortality 0 during the reperfusion period compared with saline 195 ± 42 s 71 respectivelyTargeting the delivery of liposomal amiodarone to ischemic/reperfused myocardium reduces the mortality due to lethal arrhythmia and the negative hemodynamic changes caused by amiodarone Nanosize liposomes may be a promising drug delivery system for targeting I/R myocardium with cardioprotective agentsThe authors thank Takaki Hayakawa for her technical assistance Takeshi Aiba for his special advice about data analysis This research was supported by GrantsinAid from the Ministry of Health Labor and Welfare of Japan GrantsinAid from the Ministry of Education Culture Sports Science and Technology of Japan grants from the Japan Heart Foundation and grants from the Japan Cardiovascular Research Foundation
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